James I. Mullins, Wenjie Deng, Elena E. Giorgi, Craig A. Magaret, Morgane Rolland, Tanmoy Bhattacharya, Dylan H. Westfall, Anna Yssel, Roger E. Bumgarner, Ben Murrell, Thumbi Ndung’u, Merlin L Robb, Raabya Rossenkhan, Paul T. Edlefsen, Krista L. Dong, Lennie Chen, Asanda Gwashu-Nyangiri, Hong Zhao, Ruwayhida Thebus, Nonkululeko Ndabambi, Bruna Galvao, Fredrick Sawe, Sorachai Nitayaphan, Talita York, David Matten, Hugh Murrell, Alec Pankow, Michal Juraska, James P. Ludwig, John Hural, Myron S. Cohen, Lawrence Corey, M. Juliana McElrath, Peter B. Gilbert, Carolyn Williamson
Understanding the selective forces acting upon HIV early in infection is crucial to design prevention strategies. By leveraging deep sequencing and the short diagnostic intervals of the FRESH and RV217 cohorts between the last-negative and first-positive RNA tests (median 4 days), we captured a precise and early snapshot of acute HIV infection. The frequency of multiple transmitted viruses of 37% in these as well as placebo recipients from the AMP trials (NCT02716675 and NCT02568215) was higher than previously published, with the true frequency likely to be higher. The relative abundance of lineages fluctuated substantially over time in two-thirds of the multilineage infections, generating uncertainty in identifying the specific viruses that were transmitted and founding the infection. At the population level, viral populations exhibited limited diversity and selection on the Gag and Env proteins at the earliest times examined, with sites inferred to be undergoing negative selection most evident. These data may help explain vaccination failures and provide new targets for prevention.